This is a renewal application for years 20 to 24 of the Georgetown Lombardi Comprehensive Cancer Center (Lombardi) CCSG. Lombardi's mission is to prevent, treat and cure cancers, through cutting-edge research, expert and compassionate patient care, education of future cancer specialists, and service to the community. Lombardi is the only NCI-designated cancer center in the nation's capital and in the Washington metropolitan area. The District of Columbia has among the highest cancer mortality rates in the country. Thus, there is a clear need for an NCI-designated comprehensive cancer center that can bring a targeted, evidence-based strategy to cancer care and prevention to help improve the health of the community's residents. In the present application, Lombardi comprises 177 members (113 full members), participating in six research programs with the support of 12 shared resources, based primarily in two adjacent buildings. Peer-reviewed research annual direct funding for 2008 totaled $53 million, with $28.5 million coming from the NCI. This represents a significant increase in NCI funding compared with 2002. Lombardi clinical activities are carried out in conjunction with GU's clinical partner, MedStar Health, Inc. In FY02, Lombardi clinical services served more than 22,000 outpatient cancer visits, and 603 patients were enrolled on Lombardi clinical trials. Outpatient cancer visits have increased to 39,000 in 2008, with 1,169 people placed on interventional trials. Georgetown University's (GU) unwavering high level of commitment to the success of Lombardi is exemplified by the recruitment of a new Director, Louis Weiner, MD, in January 2008. He also chairs the GU Department of Oncology, with the authority to recruit faculty, control space, and oversee resource allocation to support Lombardi's mission. Several recent high-profile recruitments attest to Lombardi's ability to attract outstanding researchers. The success of Lombardi's research environment is demonstrated by its six research programs in the areas of basic science, clinical translational research, and population science, coupled with new cross-cutting initiatives in health disparities and systems medicine. Lombardi's researchers published almost 2,000 peer-reviewed manuscripts (24% intraprogrammatic and 22% interprogrammatic) in the current funding period, exerting a sustained and powerful influence on the cancer research fields highlighted in this application, such as the development of human papillomavirus vaccines. With continued CCSG support, Lombardi will continue to make outstanding, high-impact contributions to cancer research.